Person:

Seidman, Larry Joel

Background: Early intervention services for psychotic disorders optimally interlock strategies to deliver: (i) Early Detection (ED) to shorten the time between onset of psychotic symptoms and effective treatment (i.e. Duration of Untreated Psychosis, DUP); and (ii) comprehensive intervention during the subsequent 2 to 5 years. In the latter category, are teams (‘First-episode Services’ or FES) that integrate several empirically supported treatments and adapt their delivery to younger patients and caregivers. There is an urgent need to hasten access to established FES in the U.S. Despite improved outcomes for those in treatment, these FES routinely engage patients a year or more after psychosis onset. The Scandinavian TIPS study was able to effectively reduce DUP in a defined geographic catchment. The guiding questions for this study are: can a U.S. adaptation of the TIPS approach to ED substantially reduce DUP and improve outcomes beyond existing FES? Methods/Design The primary aim is to determine whether ED can reduce DUP in the US, as compared to usual detection. ED will be implemented by one FES (STEP) based in southern Connecticut, and usual detection efforts will continue at a comparable FES (PREPR) serving the greater Boston metropolitan area. The secondary aim is to determine whether DUP reduction can improve presentation, engagement and early outcomes in FES care. A quasi-experimental design will compare the impact of ED on DUP at STEP compared to PREPR over 3 successive campaign years. The campaign will deploy 3 components that seek to transform pathways to care in 8 towns surrounding STEP. Social marketing approaches will inform a public education campaign to enable rapid and effective help-seeking behavior. Professional outreach and detailing to a wide variety of care providers, including those in the healthcare, educational and judicial sectors, will facilitate rapid redirection of appropriate patients to STEP. Finally, performance improvement measures within STEP will hasten engagement upon referral. Discussion STEP-ED will test an ED campaign adapted to heterogeneous U.S. pathways to care while also improving our understanding of these pathways and their impact on early outcomes. Trial registration ClinicalTrials.gov: NCT02069925. Registered 20 February 2014.

Siblings of patients diagnosed with schizophrenia are at elevated risk for developing this disorder. The nature of such risk associated with brain abnormalities, and whether such abnormalities are similar to those observed in schizophrenia, remain unclear. Deficits in language processing are frequently reported in increased risk populations. Interestingly, white matter pathology involving fronto-temporal language pathways, including Arcuate Fasciculus (AF), Uncinate Fasciculus (UF), and Inferior Occipitofrontal Fasciculus (IOFF), are frequently reported in schizophrenia. In this study, high spatial and directional resolution diffusion MRI data was obtained on a 3T magnet from 33 subjects with increased familial risk for developing schizophrenia, and 28 control subjects. Diffusion Tractography was performed to measure white matter integrity within AF, UF, and IOFF. To understand these abnormalities, Fractional anisotropy (FA, a measure of tract integrity) and Trace (a measure of overall diffusion), were combined with more specific measures of axial diffusivity (AX, a putative measure of axonal integrity) and radial diffusivity (RD, a putative measure of myelin integrity). Results revealed a significant decrease in Trace within IOFF, and a significant decrease in AX in all tracts. FA and RD anomalies, frequently reported in schizophrenia, were not observed. Moreover, AX group effect was modulated by age, with increased risk subjects demonstrating a deviation from normal maturation trajectory. Findings suggest that familial risk for schizophrenia may be associated with abnormalities in axonal rather than myelin integrity, and possibly associated with disruptions in normal brain maturation. AX should be considered a possible biomarker of risk for developing schizophrenia.

Background—Abnormalities in language and language neural circuitry are observed in schizophrenia (SZ). Similar, but less pronounced language deficits are also seen in young first degree relatives of people with SZ, who are at higher familial risk (FHR) for the disorder than the general population. The neural underpinnings of these deficits in people with FHR are unclear. Methods—Participants were 43 people with FHR and 32 comparable controls. fMRI scans were collected while participants viewed associated and unrelated word pairs, and performed a lexical decision task. fMRI analyses conducted in SPM8 examined group differences in the modulation of hemodynamic activity by semantic association. Results—There were no group differences in demographics, IQ or behavioral semantic priming, but FHR participants had more schizotypal traits than controls. Controls exhibited the expected suppression of hemodynamic activity to associated versus unrelated word pairs. Compared to controls, FHR participants showed an opposite pattern of hemodynamic modulation to associated versus unrelated word pairs, in the left inferior frontal gyrus (IFG), right superior and middle temporal gyrus (STG) and the left cerebellum. Group differences in activation were significant, FWE-corrected for multiple comparisons (p<0.05). Activity within the IFG during the unrelated condition predicted schizotypal symptoms in FHR participants. Conclusions—FHR for SZ is associated with abnormally increased neural activity to semantic associates within an inferior frontal/temporal network. This might increase the risk of developing unusual ideas, perceptions and disorganized language that characterize schizotypal traits, potentially predicting which individuals are at greater risk to develop a psychotic disorder.